Rapport Therapeutics' RAP-219 Trial Meets Primary Endpoint with High Statistical Significance.

Rapport Therapeutics announced the Phase 2a clinical trial of RAP-219 for drug-resistant focal onset seizures met its primary endpoint with a statistically significant reduction in long episodes (LEs) and a 77.8% reduction in clinical seizures (p=0.01). The trial also showed 24% of patients achieved seizure freedom for the 8-week treatment period (p<0.0001). The company plans to advance RAP-219 into Phase 3 registrational trials.

Boston and San Diego, September 02, 2025 — Rapport Therapeutics, Inc. (Nasdaq: RAPP), a clinical-stage biotechnology company focused on discovering and developing small molecule precision medicines for neurological and psychiatric disorders, announced positive topline results from the Phase 2a clinical trial of RAP-219 for drug-resistant focal onset seizures. The trial met its primary endpoint, demonstrating a statistically significant reduction in long episodes (LEs) and a 77.8% reduction in clinical seizures (p=0.01) over the 8-week treatment period. Additionally, 24% of patients achieved seizure freedom (p0.0001).

The Phase 2a clinical trial, a proof-of-concept, multi-center, open-label study, enrolled 30 patients with drug-resistant focal onset seizures who had an implanted RNS® System. Patients received RAP-219 oral tablets daily for 8 weeks. The primary efficacy endpoint was the change in frequency of RNS-recorded long episodes (LEs) in patients with focal onset seizures, evaluated as the proportion of responders achieving ≥ 30% reduction in LEs from baseline and median percent change from baseline in LE frequency.

Key efficacy results include:
- 85.2% of patients achieved ≥ 30% reduction in LEs from baseline (p0.0001).
- 72.0% achieved ≥ 50% reduction in clinical seizures from baseline (p0.0001).
- 24% of patients achieved seizure freedom (p0.0001).

The trial also demonstrated that RAP-219 was generally well-tolerated, with the majority of treatment-emergent adverse events (TEAEs) being mild and a low discontinuation rate.

Dr. Jeffrey Sevigny, M.D., chief medical officer of Rapport, commented, "The efficacy data and tolerability profile seen in the Phase 2a trial demonstrate RAP-219’s potential to be an important treatment for patients with drug-resistant focal onset seizures. The magnitude of the reduction in clinical seizure frequency and the corroboration of the clinical activity from the objective biomarker give us confidence that a medication like RAP-219 has the potential to be a highly effective antiseizure medication."

Abe Ceesay, chief executive officer of Rapport, added, "With these data and RAP-219’s emerging best-in-class profile, if approved, we believe RAP-219 could address a significant unmet need among patients, with the potential to support broad adoption among epileptologists and neurologists treating patients living with drug-resistant focal seizures."

Rapport plans to hold an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2025 and initiate two Phase 3 pivotal trials in the third quarter of 2026.

References:
[1] https://www.stocktitan.net/news/RAPP/rapport-announces-positive-topline-results-from-phase-2a-clinical-hpnzswrskqsl.html